Effects of nalmefene, CG3703, tirilazad, or dopamine on cerebral blood flow, oxygen delivery, and electroencephalographic activity after traumatic brain injury and hemorrhage.
Hemorrhage after traumatic brain injury (TBI) in cats produces significant decreases in cerebral oxygen delivery (DcereO2) and electroencephalographic (EEG) activity. To determine whether effective treatments for the separate insults of TBI and hemorrhagic shock would also prove effective after the clinically relevant combination of the two, we measured the effects of a kappa-opiate antagonist (nalmefene), an inhibitor of lipid peroxidation (tirilazad), a thyrotropin-releasing hormone analog (CG3703), a clinically useful pressor agent (dopamine) or a saline placebo on cerebral blood flow (CBF), and EEG activity after TBI and mild hemorrhagic hypotension. Cats (n = 40, 8 per group) were anesthetized with 1.6% isoflurane in N2O:O2 (70:30) and prepared for fluid-percussion TBI and microsphere measurements of CBF. Cats were randomized to receive nalmefene (1 mg/kg), tirilazad (5 mg/kg), CG3703 (2 mg/kg), dopamine (20 microg x kg(-1) x min[-1]) or a saline placebo (2 ml, 0.9% NaCl). Animals were injured (2.2 atm), hemorrhaged to 70% of preinjury blood volume, treated as just described and resuscitated with a volume of 10% hydroxyethyl starch equal to shed blood. CBF was determined and EEG activity recorded before injury, after hemorrhage, and 0, 60, and 120 min after resuscitation (R0, R60, and R120). CBF increased significantly after resuscitation (R0) in the nalmefene- and CG3703-treated groups. CBF did not differ significantly from baseline in any group at R60 or R120. DcereO2 was significantly less than baseline in the saline-, dopamine-, and tirilazad-treated groups at R60 and in the dopamine-, tirilazad-, and CG3703-treated groups at R120. EEG activity remained unchanged in the nalmefene-treated group but deteriorated significantly at R60 or R120 compared to baseline in the other groups. Nalmefene and CG3703 preserved the hyperemic response to hemodilution (otherwise antagonized by TBI), and nalmefene prevented the deterioration in DcereO2 and EEG activity that occurs after TBI and hemorrhage.
Dewitt
D S
DS
Department of Anesthesiology, The University of Texas Medical Branch, Galveston 77555-0591, USA.
Prough
D S
DS
Uchida
T
T
Deal
D D
DD
Vines
S M
SM
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology*; D002415:Cats; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004298:Dopamine / Q000627:therapeutic use*; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects*; D011281:Pregnatrienes / Q000627:therapeutic use*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000975:Antioxidants; D006454:Hemoglobins; D009292:Narcotic Antagonists; D018696:Neuroprotective Agents; D011281:Pregnatrienes; C031926:montirelin; D009271:Naltrexone; D013973:Thyrotropin-Releasing Hormone; C038981:nalmefene; D004298:Dopamine; C053355:tirilazad